Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 6/2/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group II drawn to method of disrupting X chromosome in a male to generate embryonically lethal female in the reply filed on 9/15/2025 is acknowledged.
Status of Claims
Claims 30-31, 34, 40, 130-145 read on the elected invention and are being examined. Claims 1-29, 32-33, 35-39, and 41-129 are cancelled.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 131 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention.
Claim 131 recites the limitation "the endogenous gene" in line 2. There is insufficient antecedent basis for this limitation in the claim.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 30-31, 34, 40, 130-145 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 30: The claim is directed to a method of altering organisms of a species by engineering a male so that the activity of an X chromosome ncRNA in the females is disrupted, resulting in female embryonic lethality in the progeny. The breadth of the claim encompasses all organisms including human subjects. However, the specification provides support for only non-human organisms, for example mice. It is submitted that the full scope of the claims are not disclosed in the specification and thus the specification is found to be lacking written description for the claimed invention.
Claims 31, 34, 40, 130-145 are rejected for their dependence on the rejected claim.
Regarding claim 40: Claim 40 requires a nuclease encoded in an endogenous gene in the Y-chromosome, where the nuclease is capable of disrupting activity of X-chromosome ncRNA. The breadth of the claim encompasses any gene in Y chromosome. However, the specification does not provide support for all genes encoded by Y-chromosome. It is known from the Chromosome map of NCBI (See attached reference, See PTO-892) that Y-chromosome contains over 200 genes. The specification states that the endogenous gene locus in Y-chromosome can be a Zfy, Ddx3y, or Eif2s3y gene. (See for example, Specification [004], [009], [010], and [0055]). It is clear that the endogenous genes in Y chromosome that were determined to be safe for fusion of nuclease were restricted to the three genes - Zfy, Ddx3y, or Eif2s3y.
Thus, Applicants were not in possession of the full scope of the claimed invention at the time of filing of the instant invention.
Claims 141-145 inherit the rejection due to their dependence on the rejected claim.
Regarding claim 34 and 131: The claim requires insertion of plurality of introns into coding region of nuclease gene, wherein the expression of nuclease with introns is increased compared to the expression without introns.
The claim is not restricted to the position of the introns (i.e.) where the introns are inserted in the nuclease, the length of the introns or the sequence of introns. As such this gives raise to enormous number of possibilities, which have no description in the specification. It is also noted that the claims encompass any nuclease for which the specification provides no support. The specification is limited to Cas9 or Cas12 nucleases. As to the position of introns, the specification did not provide any structural or functional support for the claimed level of general language in the claims.
Thus, Applicants were not in possession of the full scope of the claimed invention at the time of filing of the instant invention.
Claims 138-140 inherit the rejection due to their dependence on the rejected claim.
Claims 34, 40, 131, and 136-145 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant's specification is found enabling for insertion of Cas9 or Cas12. It is also indicated that the specification is found to be enabling for integration of Cas9 and Cas12 into the Zfy, Ddx3y, or Eif2s3y gene loci. However, Applicant's specification is not found to be enabling for the claimed breadth of claims 34, 40. For example, the specification is not found to be enabling for:
any nuclease.
integration of any nuclease to any Y-chromosome gene.
integration of plurality of introns of any length at any position in any nuclease.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to carry out the method of the invention commensurate in scope with the current claims.
Analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention without undue or unreasonable experimentation. See Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916). The key word is 'undue,' not experimentation.' " (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
Applicants' claims are directed to :
any nuclease.
integration of any nuclease to any Y-chromosome gene.
integration of plurality of introns of any length at any position in any nuclease.
The breadth of the claims includes non cas9 or CRISPR genes. Further, the breadth of the claims includes integration of nuclease in any Y-chromosome gene. Further, the breadth of the claims includes integration of introns of any size into any position of the nuclease that increases the expression.
The specification provides support for deletion of a small segment of Xist exon 1 that encodes critical repeated stem-loop motifs, a minimal number of which are strictly required for X-inactivation in mice for population control using CRISPR/scCas9. The specification provides support for development of a protocol comprising steps of sequencing genome, identification of critical xist stem-loop; analysis of target sites for an RNA-guided nuclease in the region Nuclease activity on the target sites and off-targets is tested in cells, identification of a promoter and downstream elements for expression of nuclease, and generating engineered organisms.
At the time the invention was made several nucleases and methods of disrupting a gene in the chromosome were known which included use of nucleases such as endonucleases, meganucleases, TALENs. Additionally several CRISPR nucleases were known. Such nucleases were known to be structurally and functionally different. The specification does not provide guidance to a person of ordinary skill in the art to choose an appropriate nuclease for the purposes of the invention. Therefore there was a recognized level of unpredictability with regards to the nuclease.
Further, the specification did not teach integration at any and all gene loci of Y chromosome. It is known by a person of ordinary skill in the art that not all genes in Y-chromosome are available for gene integration or translational fusion of a protein. For example, as evidenced by Rogers (See PTO-892) “[t]he Y chromosome is unique in that the majority of its structure is highly repetitive sequences, with the majority of these limited genes occurring in 9 amplionic sequences throughout the chromosome. The repetitive nature has its benefits as it can be protective against gene loss over many generations, but it can also predispose the Y chromosome to having wide variations of the number of gene copies present in these repeated sequences. This is known as copy number variation. Copy number variation is not unique to the Y chromosome but copy number variation is a well-known cause of male infertility and having effects on spermatogenesis.” Rogers further disclosed that “Copy number variations of TSPY1, DAZ, CDY1, RBMY1, the DYZ1 array, along with minor deletions of gr/gr, b1/b3, and b2/b3 have all be implicated in affecting spermatogenesis.” (See Rogers Abstract). As such, all genes in Y-chromosome would not have been available for insertion of nucleases. To practice the invention, one of ordinary skill in the art would have to incorporate one of many nucleases into more than 200 genes in Y-chromosome and probe for undesirable phenotypes. Therefore there was a recognized level of unpredictability with regards to the nuclease integration into a suitable Y-chromosome gene. The specification indicates that “Computational analysis is performed on target sites for an RNA-guided nuclease in the region.” However, the specification is silent with respect to what parameters are used as input and which parameters are measured as output. As such, the specification does not provide insight into computational analysis or provide appropriate guidance to choose a Y-chromosome gene.
Further the specification did not provide any support for which region of each known nuclease (or even just Cas9/Cas12) are used for insertion of intron. The specification cited Tikhonov et al (See PTO-892) as a guidance for insertion of introns. It is noted that Tikhonov is directed to splicing in CHO cells, which are entirely different from the target cells of the invention. (See Tikhonov p, 595 col. 1, para 2). Further, the Tikhonov did not teach a general rule for insertion of donor and acceptor sites, branch point for all genes, and particularly nucleases. It is difficult to extrapolate the findings of Tikhonov to all proteins or indeed all organisms and all regions of all proteins. As such the specification did not provide a method of determining an insertion site, length of the intron, or describe where and how gRNAs will be added as claimed in claim 138. To practice the invention, a person of ordinary skill in the art, according to the method laid out by Tikhonov should map thousands of intronic regions, find optimal distribution of distances between the branch point and the acceptor site, find an optimal amino acid residue from where to engineer the intron, optimize the length of intron. As such there is no guidance in the specification for any of the steps involved. Therefore there was a recognized level of unpredictability with regards to the nuclease.
Due to the lack of teachings in the art regarding each of the above mentioned elements, the recognized unpredictability, a large amount of guidance and teachings would be necessary in order to be enabling for methods of such.
Guidance and teachings provided by Applicants in the instant specification is limited to disclosure that integration of Cas9 and Cas12 into the Zfy, Ddx3y, or Eif2s3y gene loci. The Examiner acknowledges that the Office does not require the presence of working examples to be present in the disclosure of the invention (see MPEP §2164.02). However, in light of the state of the art, discussed above, which recognizes a high level of unpredictability in the field of molecular biology, and genetics, , and limited teachings in the specification, the Office would require appropriate disclosure to support the contention that the specification is enabled for the claimed invention in claims may be successfully employed in the methods of claims 34, 40, 131, 138-145. The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Thus, due to the high level of unpredictability in the art, the current specification would have to provide greater amounts of teachings and guidance directed to methods of carrying out the claimed invention.
Therefore, due to the sum of all the aforementioned factors, one of ordinary skill in the art, at the time the invention was made, would not expect success carrying out the indicated claimed methods Accordingly, claims 34, 40, 131, 138-145 are deemed properly rejected.
Claim Rejections - 35 USC § 102
Claims 30-31, 132-133 and 135 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Marahrens et al (hereinafter "Marahrens;" Genes Dev. 1997 Jan 15; See IDS of 6/2/2023).
Regarding claims 30-31, 132-133 and 135: Marahrens was directed to investigation of X-linked Xist gene, which encodes a large untranslated RNA that has been implicated in mammalian dosage compensation gene product. (Marahrens Abstract). Marahrens disclosed “a targeting construct was designed to replace -15 kb of the Xist gene with the neomycin resistance gene, leaving the promoter intact.” (Marahrens p. 157, col. 1, last para). Marahrens further introduced the targeting construct into male ES cell lines and used the “Xist-deficient ES cells were used to generate 17 chimeras that were identified by the presence of agouti coat color and black eyes produced by the targeted 129 cells against an albino host background.” (Marahrens p. 157, col. 2, 2nd para) Marahrens “crossed male chimeras to female albino mice. Of the 13 males, 11 sired pups with dark fur demonstrating that Xist-deficient cells can undergo spermatogenesis. Three of these male chimeras exclusively sired pups with dark fur. The three chimeras were fully fertile indicating that spermatogenesis was not impaired. The pups descended from cultured ES cells appeared normal and healthy. Significantly, all of the pups were male with one exception: a female that was determined to be XO.” (Marahrens p. 157, col. 2, 3rd para). Further Marahrens explicitly stated that “The observations described above indicated that females inheriting the Xist mutation die after cleavage.” (Marahrens p. 157, col. 2, last para). As such Marahrens disclosed a method to alter an organism by engineering a male, where activity of an X-chromosome non-coding RNA gene is disrupted in female descendants and where crossing the altered male with a female results in disruption of non-coding RNA is embryonically lethal to females.
Claims 30, 34, 130 and 136-137 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Galizi et al (hereinafter "Galizi;" Sci Rep 6; Published 2016; See PTO-892) further as evidenced by Vydzhak et al (hereinafter "Vydzhak;" J Mol Biol. 2020 Jul 10; See PTO-892).
Regarding claim 30, 34, 130 and 136-137: Galizi taught a CRISPR-Cas9 sex distortion (CRISPRSD) method for population control. Galizi utilized the CRISPR-Cas9 nuclease to target an X-linked rDNA sequence. (See Galizi p. 1, 2nd para). It is noted that rDNA codes for a non-coding rDNA as evidenced by Vydzhak (See Vydzhak Abstract). Galizi “designed a germline transformation construct where the Cas9 endonuclease coding sequence was placed under the transcriptional control of the spermatogenesis-specific β 2 tubulin promoter,” restricting “the endonuclease activity to male meiosis” (See Galizi p. 1, last para). Galizi disclosed that “All the CRISPRSD lines showed a strong sex-ratio distortion, with a male bias among progeny ranging from 86.1% to 94.8% of males. The fertility of hemizygous transgenic males was also tested revealing full fertility from three of four strains” (See Galizi, p. 2, para 2). Galizi disclosed that “genetic linkage of the sex distorter transgene with the Y-chromosome (Fig. 3c) would ensure that the distorter increases in frequency with each generation since it would be present in all male progeny, resulting in a self-perpetuating genetic trait that could rapidly invade and suppress, perhaps eliminate, a natural population even if initially seeded at a very low frequency.” (See Galizi, Fig. 3c, p. 3, 1st para). Thus it is noted that Galizi disclosed releasing engineered male into target population as required by claim 130. It is specifically noted that Figure 3c of Galizi disclosed placing Cas9 in the Y-chromosome, that resulted in 100% male progeny. It is submitted that all aspects of the claim are anticipated by the disclosure of Galizi.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 30, 133-134 and 139-140is/are rejected under 35 U.S.C. 103 as being unpatentable over Marahrens et al (hereinafter "Marahrens;" Genes Dev. 1997 Jan 15; See IDS of 6/2/2023); and Galizi et al (hereinafter "Galizi;" Sci Rep 6; Published 2016; See PTO-892) in view of Wutz et al (Hereinafter "Wutz;" See IDS 6/2/2023) further as evidenced by Vydzhak et al (hereinafter "Vydzhak;" J Mol Biol. 2020 Jul 10; See PTO-892).
Regarding claims 30, 133-134 and 139-140: The teachings of Galizi and Marahrens are set forth above. Galizi taught encoding Cas9 in the Y-chromosome for targeting rDNA-based sex distortion in population control. Marahrens taught the use of XIST in conferring female embryo lethality. However, Galizi and Marahrens did not specifically teach that the nuclease cuts in the stem-loop region of the X-chromosome ncRNA gene as required by claim 130. Wutz was directed to elucidating which Xist RNA sequences are necessary for chromosomal association and silencing. (See Wutz Abstract). Wutz taught that, if “the stem loop was destroyed by two base changes predicted to disrupt base pairing (Fig. 6b, construct XNX), silencing was not initiated. This indicated that the first stem loop is essential but the sequence of its stem is not crucial for function.” Wutz additionally taught that “[r]emoval of the second stem loop (construct XS1 in Fig. 6b) resulted in loss of function, indicating that both stem loops of the repeat monomers are essential for silencing.” As such Wutz taught that the importance in preservation of the stem-loop structure in A region of XIST gene. As such it would have been obvious for a person of ordinary skill in the art at the time of invention to combine the teachings of Galizi, Marahrens and Wutz b selecting Xist gene as a target for effecting female embryo lethality. Further, the person would have also been motivated to destroy one of the stem-loop of Xist gene, because as taught by Wutz, the stem loop structure is crucial for activity of XIST. The motivation to combine arises from the common objective of the Galizi, Marahrens and Wutz which was directed to female embryonic lethality and the function of Xist gene. It is also recognized that disrupting stem-loop in Xist comprises cutting on both sides of a stem loop or cutting within a stretch of stem loop as required by claims 139-140.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 30, 31, 34 and 131 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over pending claims of copending Application No. 17/778,482 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the reasons indicated below.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 30: claim 25-26 of the reference application reads on a daughterless male heritable trait introduced into a target population, wherein the activity of X-chromosome ncRNA in a female is disrupted. As such all elements of the claim are disclosed.
Regarding claim 31: claim 27 of the reference application discloses impregnating a female with the genetically engineered male.
Regarding claim 34: claim 29 of the reference application discloses use of nuclease in Y-chromosome.
Regarding claim 131: Claim 76 of the reference application discloses releasing the male into a target population.
Conclusion
Claims 40, 139 and 141-145 appear free of art, but lack written description and enablement.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M. Babic can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/ Primary Examiner, Art Unit 1633